Are We in the Same Risk of Diabetes Mellitus? Genderand Age-Specific Epidemiology of Diabetes in 2001 to 2014 in the Korean Population

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1 Review Epidemiology Diabetes Metab J 216;4: pissn eissn DIABETES & METABOLISM JOURNAL Are We in the Same Risk of Diabetes Mellitus? Genderand Age-Specific Epidemiology of Diabetes in 21 to 214 in the Korean Population Bo Kyung Koo 1,2, Min Kyong Moon 1,2 1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 2 Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea In the early 2s, the prevalence of diabetes in adults aged 3 years in Korea was about 9% to 1%, and it remained stable. However, a nationwide survey showed that this prevalence increased over the past few years. After age-standardization using the Korean population of the year 21, the prevalence of diabetes in adults aged 3 years was 1.% to 1.8% between 21 and 212, which increased to 12.% in 213 and 11.6% in 214. During that period, there have been changes in the gender- and agespecific prevalence of diabetes in Korean adults. The prevalence of diabetes in the elderly population increased significantly, while this prevalence in young adults, especially in young women, did not change significantly. The contribution of each diabetic risk factor, such as obesity, β-cell dysfunction, sarcopenia, and socioeconomic status, in developing diabetes has also changed during that period in each gender and age group. For young women, obesity was the most important risk factor; by contrast, for elderly diabetic patients, sarcopenia was more important than obesity as a risk factor. Considering the economic burden of diabetes and its associated comorbidities, a public health policy targeting the major risk factors in each population might be more effective in preventing diabetes. Keywords: Diabetes mellitus; Korea; Obesity; Prevalence; Sarcopenia INTRODUCTION The International Diabetes Federation estimated the global prevalence of diabetes to be 1 million in 2 [1] and 28 million in 21 [2]. This prevalence is expected to rise to 2 million by 23 [3]. In Korea, after a rapid increment of the prevalence of diabetes during the last 3 years, the prevalence of diabetes in adults aged 3 years reached about 9% to 1% and remained stable between 2 and 21 [4,]. A recent Korea National Health and Nutritional Examination Survey (KNHANES) 211 to 214 showed that the prevalence of diabetes in adults aged 3 years increased to 1% to 11% [6]. During that period, along with the trend of an increasing number of elderly people in Korea [7], the number of elderly patients with type 2 diabetes mellitus (T2DM) increased significantly [8,9]. In addition, the gender disparity in the trend of the prevalence of diabetes and obesity was apparent in the 2s [9,1]. In this review, we summarized the recent trends in the prevalence of diabetes in Korea, and the risk factors associated with those trends will be discussed. THE PREVALENCE OF DIABETES The prevalence of diabetes in Korean adults aged 3 years Corresponding author: Min Kyong Moon Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, 2 Boramae-ro -gil, Dongjak-gu, Seoul 761, Korea mkmoon@snu.ac.kr Received: Apr. 11, 216; Accepted: May 9, 216 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 216 Korean Diabetes Association

2 Koo BK, et al. 2 Women aged 3 years Men aged 3 years Total ( 3 years) 4 Aged 3 9 years Aged 6 years Fig. 1. The age-standardized prevalence of diabetes in adults aged 3 years from the Korean National Health and Nutrition Examination Survey 21 to 214. Age standardization was done using the Korean population in the year 21. Cases of diabetes mellitus were defined as subjects who were users of antidiabetic medication, including insulin, at the point of the survey or had 8-hour fasting plasma glucose levels 126 mg/dl. (A) The overall prevalence of diabetes mellitus in adults aged 3 years was shown according to gender. The prevalence in men and women was presented by a circle and square with a standardized error bar, respectively. (B) The prevalence of diabetes mellitus in adults aged 3 to 9 years and 6 years was presented with black and gray bars, respectively Year A Men Women B remained stable at approximately 9% to 1% between 2 and 21 [4,]. The Korean Centers for Disease Control and Prevention reported that it increased to 1% to 11% between 211 and 214 [6]. If cases of diabetes mellitus (DM) were defined as subjects who were users of antidiabetic medication, including insulin, at the point of the survey or had 8-hour fasting plasma glucose levels 126 mg/dl, the age-standardized prevalence of diabetes using the Korean population in the year 21 was 1.% to 1.8% in adults aged 3 years during 21 to 212, which increased to 12.% in 213 and 11.6% in 214 (Fig. 1A). In men, age-standardized prevalence in 213 and 214 was 13.7% and 13.1% respectively; in women, that was 11.% and 1.3%, respectively (Fig. 1A). The agestandardized prevalence in subjects 3 to 9 years old did not change much between 2 and 214: 8.3% to 1.2% in men and 4.3% to.9% in women (Fig. 1B). By contrast, the elderly population aged 6 years showed an increasing trend of diabetes prevalence from 19.% in 21 to 21.4% in 21 and to 24.7% in 214 (Fig. 1B). Since 211, all adult participants in the KNHANES had their glycosylated hemoglobin (HbA1c) level measured following the guidelines of the Korean Diabetes Association, which adopted an HbA1c 6.% as a diagnostic criterion for DM since 211 [11]. Considering that in the previous KNHANES, only participants who had a medical history of diabetes measured their HbA1c level, a trend in the prevalence of diabetes estimated from the KNHANES should be interpreted with caution. After adopting an HbA1c 6.% as one of the diagnostic criteria of diabetes, the prevalence of diabetes was increased 2.2% to 2.4% (Fig. 2) as previously reported [12]; the agestandardized prevalence of diabetes in adults aged 3 years reached 13.2%, 12.3%,.6%, and 13.8% in 211, 212, 213, and 214, respectively (Fig. 2). Nationwide claim data showed that the peak incidence of T2DM between 28 and 21 was observed at 6 to 79 years of age (i.e., 23 to 2/1, person-year [PY]) both in men and women (Fig. 3) [8]. In men, the incidence of diabetes in individuals to 9 years old and 8 to 89 years old was next (18/1, PY). In the case of women, the incidence of diabetes in individuals 8 to 89 years of age was next (17/1, PY). Women aged to 9 years old showed a relatively lower incidence of diabetes than men of the same age (13/1, PY vs. 19/1, PY) [8]. Korea is one of the most rapidly aging countries; the proportion of the elderly population aged 6 years reached 11.% in 21 and is expected to be 22% in 22 [7]. The increasing size of the elderly population might result in the nationwide increasing prevalence of diabetes. Considering that 176 Diabetes Metab J 216;4:17-181

3 Type 2 diabetes in Korea, 21 to Men using criteria I Women using criteria I Men using criteria II Women using criteria II Year A Year Fig. 2. The age-standardized prevalence of diabetes in adults aged (A) 3 years and (B) 3 to 9 years from the Korean National Health and Nutrition Examination Survey 21 to 214 using different diagnostic criteria. Cases of diabetes mellitus were defined as subjects who were users of antidiabetic medication, including insulin, at the point of the survey or had 8-hour fasting plasma glucose levels 126 mg/dl (criteria I, solid line). After adopting an glycosylated hemoglobin 6.% as one of diagnostic criteria of diabetes (criteria II, dashed line), the prevalence of diabetes was increased 2.2% to 2.4%. The incidence of diabetes (/1, PY) Men Fig. 3. The incidence of type 2 diabetes mellitus in the Korean population by age group from the National Health Insurance database. PY, person-year Women B the increasing prevalence of diabetes may also increase the economic burden, a public strategy targeting elderly people for diabetes prevention is urgent. In the case of the younger population, a nationwide health survey showed a relatively stable prevalence of diabetes, especially in women [9]. These results corresponded with the nationwide survey in Japan [13] but were not observed in China [14]. However, considering that only % to 6% of young diabetic patients aged 3 to 4 years have insight to have diabetes in Korea [,16], and undiagnosed diabetic patients showed a significantly higher risk of cardiovascular disease compared to diagnosed diabetic patients [], a public heath strategy targeting the younger population for diabetes screening might be needed. TRENDS IN RISK FACTORS FOR DEVELOPING DIABETES Obesity In Korea, the prevalence of obesity and abdominal obesity in Diabetes Metab J 216;4:

4 Koo BK, et al. the general population has increased from 2 to 27; it has remained steady since then [17]. However, in the cases of young women, body mass index (BMI) and waist circumference have significantly decreased during the 2s in the general population [9,1]. By contrast, in the cases of women with diabetes of the same age, the prevalence of abdominal obesity increased from 66.3% to 72.9% during the same period [18]. Along with this trend, abdominal obesity is the single most important independent risk factor for diabetes in young Korean women [18]. It was associated with more than four times a higher risk of diabetes in 21 even after an adjustment for age, dyslipidemia, family history, and exercise. The fact that abdominal obesity is the most important risk factor of diabetes in women was in agreement with a large cohort study conducted in the United States on young women during 16 years of follow-up [19]. Attributing the power of obesity or abdominal obesity for developing diabetes was more prominent at a young age compared to the elderly population in Korean women [18], as well as in Japanese women [2]. In terms of men, there might be a difference in the contribution of obesity in the development of diabetes compared to women. For the last 1 years, BMI was significantly increased in young men [9,1]. However, there has not been much change in the prevalence of diabetes in young Korean men [9]. Furthermore, in them, the association between obesity and diabetes has been attenuated [18]. In the early 2s, the prevalence of abdominal obesity in subjects with diabetes was about two times higher than that in nondiabetic subjects; however, there was no difference in the prevalence of abdominal obesity between subjects with and without diabetes in 21 [18]. Instead, the association between a family history of diabetes and DM in these subjects was much stronger in the late 2s [18]. β-cell function The main pathogenic mechanism in developing T2DM in obesity or aging is insulin resistance; however, more than 7% of obese or elderly people are free of diabetes [,17,21]. Recently, a 1-year follow-up cohort study showed that insulin sensitivity was significantly decreased with aging, regardless of the glucose tolerance state at the follow-up [22]. However, compared with participants who remained normal glucose tolerance (NGT), those who progressed to diabetes had a lower β-cell function [22], which agreed with previous reports in Japan [23] and a multiethnic population [24]. They have suggested that impaired β-cell function might be the determining factor whether or not T2DM develops or the condition of insulin resistance increased. The main determinants of β-cell function in T2DM is genetic factor associated with the insulin secretion capacity and the proliferation and regeneration of β-cells [2]. A long-term cohort study in Korea also confirmed that a genetic variant near the glucokinase gene was significantly associated with the progression to diabetes [22]. In terms of age of onset, β-cell dysfunction might be more important in people with early-onset diabetes compared to elderly-onset diabetic patients [26], which was also reproduced 2 Subjects with recent-onset DM Subjects without DM 8 Subjects with recent-onset DM Subjects without DM 6 HOMA-β 1 HOMA-IR A Fig. 4. The level of (A) insulin secretion capacity and (B) insulin resistance according to the age of patients with recent-onset diabetes from the Korean National Health and Nutrition Examination Survey 28 to 21. Recent-onset diabetes patients were defined as those who have had diabetes for < years. HOMA-β, the homeostasis model assessment of β-cell function; HOMA- IR, the homeostasis model assessment of insulin resis tance; DM, diabetes mellitus B 178 Diabetes Metab J 216;4:17-181

5 Type 2 diabetes in Korea, 21 to 214 in Korea [27]. Among people with recent-onset diabetes from the KNHANES, defined as those who have diabetes for < years, there was an inverse correlation between age and the homeostasis model assessment of β-cell function (Fig. 4). In addition, young diabetic patients were more influenced by a family history of diabetes compared to elderly patients [18], which was in agreement with Caucasians [28]. That association was more prominent in men. In young men, a family history of diabetes was associated with more than six times a higher risk of diabetes [18]. In the case of women of the same age, however, the presence of obesity but not family history was the most important determinant of diabetes status [18]. Sarcopenia A decrease in the insulin sensitivity with the aging is well known, even in individuals who remained as NGT at 1 years [22], which can be partially explained by decreased muscle mass (i.e., sarcopenia, along with increased fat mass). The KNHANES 28 to 21 showed that for elderly-onset diabetic patients, insulin resistance was more prominent compared to middle-age-onset patients at the time of diagnosis [27]. Although insulin resistance was higher in the elderlyonset diabetic patients compared to the middle-age-onset patients, the BMI, waist circumference, and body fat mass of the elderly-onset subjects were not different across the age group, which was in agreement with the Chinese population [29]. In a cross-sectional study comparing Caucasian and Chinese patients with recent-onset diabetes (duration <2 years), a negative correlation between the age at diagnosis and BMI or insulin resistance was only observed in Caucasians. In Chinese diabetic patients, there was no relationship between age at diagnosis and BMI, insulin resistance, or triglyceride level [29]. Instead, a Korean nationwide survey showed that elderlyonset diabetic patients had significantly lower skeletal muscle mass and higher prevalence of sarcopenia compared with the middle-age-onset group [27]. Comparing the elderly-onset diabetic patients with the age-matched NGT subjects (although there was no difference in the sarcopenia class I prevalence) (milder form of sarcopenia; 1 to 2 standard deviations below the gender-specific mean for healthy young adults), the advanced stage of sarcopenia (>2 standard deviations below the gender-specific mean for healthy young adults; classified as class II) was found about three times more frequently in those with recent-onset diabetes compared with nondiabetic subjects (Fig. ). Prevalence of sarcopenia (%) Recent-onset DM No DM Class I Class II 7 Fig.. The prevalence of sarcopenia (class I+class II) in subjects with recent-onset diabetes and without diabetes. Sarcopenia was classified as class I or class II, defined as appendicular skeletal muscle mass/weight 1 to 2 or >2 standard deviations, respectively, below the gender-specific mean for healthy young adults. The entire prevalence of sarcopenia in each age group was separated by gray and black bars which represent the prevalence of sarcopenia class I and II, respectively. DM, diabetes mellitus. Socioeconomic status Low socioeconomic status (SES) is a well-documented risk factor of diabetes in developed countries [3,31]. Korea is one of the most rapidly developing countries in the world [32]; low SES has been an emerging risk factor for DM in recent years [33-3]. Both low income status and low education level were significantly associated with the risk of diabetes in the KNHANES 28 to 212 even after an adjustment for other risk factors (i.e., obesity and dyslipidemia) [33,34], which was not observed in 21 or 2 [33]. In other Asian countries, such as India and China, the same tendency was also observed [36,37]. In addition, the association between SES and diabetes was prominent in people less than 6 years old [33,3]. Poorer and less educated people have fewer opportunities for primary prevention, early diagnosis, and appropriate management [38]; however, these disadvantages can be overcome [31,39]. Low SES is also associated with a high prevalence of obesity [33,37]. The reduction of obesity in populations with a lower SES has proven to be successful for preventing diabetes in India [37], which might be another possible strategy for reducing health inequality according to SES. Diabetes Metab J 216;4:

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